To explore the mechanisms by which androgens act to induce masculinization of the male urogenital tract during embryogenesis and to virilize the male at the time of puberty, a variety of projects are planned to include a continued exploration of the enzymology of the 5 alpha-reductase enzyme that converts testosterone to dihydrotestosterone, an analysis of the molecular defects that give rise to male pseudohermaphroditism utilizing both cultured human fibroblasts and the Tfm mouse, a biochemical dissection on the 8S dihydrotestosterone binding protein of cytosol and a study of the regulation of its activity, a genetic analysis of the regulatory genes that mediate androgen action in the mouse, a study of cellular differentiation using both the differentiated fibroblast in tissue culture and the embryonic Leydig cell as models, a continued exploration of the nature of the role of dihydrotestosterone in androgen action with special emphasis on the concept of estrogen-androgen balance, and feasibility studies to determine whether the current concepts of the pathogenesis of defective sexual development in man can be applied to common birth defects such as hypospadias and for identification of heterozygotes at risk for the various mutant genes. Thus, a multifaceted approach is projected to provide insight into androgen action in the normal and into the pathophysiology of male sexual development as well.